Treating Type 2 Diabetes without Surgery or Drugs | Pankaj “Jay” Pasricha, M.B.B.S., M.D.

Treating Type 2 Diabetes without Surgery or Drugs | Pankaj “Jay” Pasricha, M.B.B.S., M.D.

Thank you, Steve. It’s always a pleasure,
as a gastroenterologist, to give a talk after everybody’s
come back from a full meal.>>[LAUGH].>>I’m not sure if
the pleasure goes both ways, depends on what you ate. But what I’m gonna talk to you
about today is a different way of looking at a disease
that you’re all familiar with. Type 2 diabetes. I’d like you to focus on the
role of the gut by walking you through the evolution of our own
thinking in some innovations that I will present today. So, okay sorry. I think. So you’re familiar
with these graphs. They tell a disappointing and
distressing story. This is the rising prevalence
of diabetes in this country. As you may have already heard, there are about 28 million
Americans with Type 2 Diabetes. And 86 million of them in what
we call the pre-diabetic phase. Not yet classified as
having the disease, but they’re well on their way
to becoming diabetic. It comes, of course,
with a huge economic cost. But more importantly, if you think about
the statistics, a third of all Americans will be diabetic
if this trend continues. And this trend is not only
relevant in this country. There are some countries in some
regions of the world such as the Middle East or South Asia where the trend
is even more alarming. 50% or more of patients, of citizens in those regions,
may become diabetic. So this is really a huge crisis,
and something that we need to do more than what
we’ve been doing so far. I think the first half of today
was on weight management. And clearly, there is a relationship
between weight and diabetes. And this is what’s driving
the diabetes epidemic. I purposely used a very, very old slide because this was
a paper that came here from the Harvard School of Public
Health about 20 years ago. And has really set the stage for how we think about
the relationship between weight and diabetes. You can see here on the x
axis is the amount of weight that you gain since you
were 21 years of age. And with each five kilos, or
roughly ten or twelve pounds, your risk of developing
diabetes rises, and within these categories,
if you are already overweight to begin with, as you can see by
the BMI, it rises even further. So if you gain about 20
plus pounds since you were at the age of 21 and
your BMI is at 24 or plus, then you have
almost a 20-fold increased risk of
developing diabetes. We also know that the principle
mechanism by which weight gain, particularly the accumulation of
what we call visceral fat, which is the fat around your visceral
organs or your internal organs, is related to the development
of insulin resistance. So insulin, as you know, is the hormone that drives
sugars inside the cells. And insulin resistance refers
to the phenomenon in which the cells don’t respond as
well as healthy cells do. So you need actually a lot more
insulin to drag the sugars into the cells, which then results in rising
sugar levels in the blood. So for a long time,
this relationship has been recognized, and it has led to
this so-called great debate. We must reduce weight. And until now there were
only two real choices, either pills, and we know that pills don’t work
very well for losing weight. Or you put them on
diabetic medications. And in the last ten years or so,
we also now know that there is a very effective surgical
option for these patients. But it’s a very drastic option,
and this is gastric bypass surgery. You’re familiar with this. Other people have talked
to you about this. It’s the creation of
a small gastric pouch, and then diversion of
the food contents away from the rest of
the stomach and the duodenum. And this is the area
that is bypassed, and that’s why this is
called a bypass operation. It is extraordinarily effective
in treating diabetes, not just weight loss. In the beginning,
we thought the salutary effects on diabetes were due
to the weight loss. But then we started noticing
that patients were walking out of the hospital within a few
days of their surgery, throwing away their insulin. This was before they’d lost
even a pound of weight. And this is when the modern era
of thinking about Type 2 disease as a surgical problem start. So I’m not going to go into the
details of these studies, but these are three critical studies
that I’ve shown that after gastric bypass surgery three
years later, for instance, 87% of patients could
come off insulin. Similarly other
studies have shown equally impressive results. So what have we
learned from this? To sum up a lot of
the experimental literature, the take home lesson is this is
the critical piece of surgery responsible for
the anti-diabetic effect. So bypassing the duodenum
appears to be the most useful target for
treating diabetes. If you exclude the duodenal
wall from contact with food, so called intraluminal contents, we
can, in fact, defeat diabetes. This lesson has now been studied
very well in animals, and there are some interesting theories
as to what the duodenum, which is the first part of
the gut after the stomach, is doing to control diabetes. We still are not
completely sure. Work in my lab has shown that
it’s probably the nerves off the duodenum that
are responsible for this effect. Other people speculate
that there is as yet identified hormones, so
called anti-incretins. Incretins are the hormones that
help with the production of insulin and this, as yet
unidentified anti-incretin, is a hormone that
works against insulin. And it is postulated that if
the duodenum does not come into contact with food, then this
anti-incretin is suppressed and therefore you have
an amelioration of the diabetes. But these are really
theories and I don’t want to spend a lot of
time on this because much of this work still
needs to be done. Nevertheless, it has translated into some
real practical solutions. Even though we don’t fully
understand how it works. And one of the first
successful devices that exploited this particular
property was a sleeve, it’s called an EndoBarrier, made by this company,
GI Dynamics. So they came up with
this relatively simple, I would say brilliant, solution. If all we need is to exclude
that part of the gut from food contents,
why go through surgery? Why not put a liner in there,
essentially a sleeve. Food travels through
that sleeve, does not come into contact with
the lining of the duodenum and may achieve the same
effect as bypassing that part of
the duodenum surgically. So, in fact, it worked, much to the surprise
of a lot of us in the field. It worked and
it worked very well. It got approval in Europe,
the so called CE mark, which is the rough equivalent of what
the FDA does in this country. And then they started a pivotal
trial here In the US to try and obtain FDA approval. And before I tell you what
happened with that story, I just wanna show you something
that came off the wire this morning from the company. This is a result of the UK trial just to illustrate
how effective it is. This trial is
a little different. They used it in combination
with a drug that works for type 2 diabetes, and you can see with the combination
of the sleeve and the drug, they had significant improvement
in a variety of factors. So if you look at the number of
subjects who had at the end of 12 months less than 7.5
units of hemoglobin A1C, which is considered very good. It’s not ideal but it’s very
good for type 2 diabetes. Nearly 50% or
more of these patients achieve that goal compared to only
about a third of them, a third just on the drugs alone. So this is very good news, so
you say what is the downside? Right? And the downside is that when
they started the trial in this country, they had to
stop it about a year ago. And they had to stop it because
of the development of side effects. Now, there are lots of side
effects of the sleeve, including some shown here. But the one that they had
to suspend the trial for was a very serious side effect,
what we call a liver abscess. It was an abscess that occurred
in the liver of these patients. It was focal collection of
infection that occurred in these patients. Potentially life threatening,
but certainly requiring intervention in the form
of intensive antibiotics. So this trial had been
halted because there was an unexpectedly
high number of patients developing hepatic abscess. The company was a publicly
traded company. It was down to its
last few bucks, a few million bucks I guess, but that’s the same thing as far
as this company is concern.>>[LAUGH]
>>They couldn’t really run their trial, it was thought that
this company would have a fire sale and basically go bankrupt. But apparently, they still
have faith in this, and they’re going to revive this, perhaps with some additional
features that’ll make it safer. So this chapter is
not fully closed, although it’s somewhat
disappointing. But in the next year or so,
you might see this sleeve reemerge as a potential
viable alternative. So we went from gastric bypass,
major surgery, nobody really wants it if they can help it, to
something that is much simpler, endoscopically placed sleeves. So this was not done surgically, nobody had to get their
abdomens opened up. Just take a simple endoscopic
procedure, pop the sleeve down, very appealing. And then this company Fractal,
which was started by a cardiologist,
took it one step further. They said well, maybe,
it’s not about excluding, well, it is about excluding
the duodenal lining. But what if we just go to
the heart of the matter, and modify the duodenal lining? What if we induced changes in
the duodenal lining that make it permanent, the inability
to respond to food? This is Fractal, and they came
up with a relatively simpler procedure than the sleeve,
which is to go in and literally burn the lining
of the duodenum. When you burn the lining
of the duodenum, then the duodenum
eventually does heal. And when it heals,
they anticipate the so-called remodeling of the lining
into a state which is no longer as responsive to food as
it used to be, and therefore, potentially mimics the effects
of gastric bypass surgery. And they don’t have controlled
clinical data yet, but from their initial studies, it does
appear that this might work. There are, of course, some risks
to this, because when you burn the lining of a duodenum, what
you create is a duodenal ulcer, and so there are risks
associated with that. How they can manage that,
and whether or not this kind of remodeling
that they are speculating on is actually sustained beyond
a few months is also not clear. But it’s an example of how
creative people are getting, now that they know
what the target is. So here is the gap, right. So if you look at costs and you
look at the efficacy in terms of the ability to reduce hemoglobin
A1c, we have surgery right at the top, very expensive but
also very morbid, lots of problems associated
with gastric bypass surgery. Clearly, it’s not
an ideal solution for a variety of reasons. You have oral meds and insulin
which are relatively cheaper in the scale, but
certainly not as effective. And then you have these emerging
treatments that are still gonna be expensive, require some kind of procedure
even if it’s not surgery. And they may have side effects
like we talked about and like the ones that I showed you
in terms of the hepatic abscess. So here’s a gap that
needs to be filled. And of course,
medical innovations, like nature abhors a vacuum,
medical innovation abhors a gap. So lots of people
are trying to fill this. What do we need
to fill this gap? We need something that’s
actually completely noninvasive. Eliminate the specialist,
we don’t need to go to a gastroenterologist
to get this done, or we don’t need to go to
a surgeon to get this done. Your GP should be able to
deliver this treatment. That’s another
important requirement. But works the same principle
as surgery, in other word, mimics surgery. And even if there’s a trade-off,
even if it’s not as effective as surgery, but if it’s simple,
cheap, easy to administer, convenient, lots of people
will benefit from that. So with that as background,
I wanna tell you a little bit about this company
that I helped cofound. And this came out of one of the
foremost schools of biodesign or courses of programs of
biodesign in the country. And that is the Hopkins CBID
program, which stands for Center for Biodesign Innovation. And Tom Donner, who is
gonna be speaking after me, was an advisor to this
group of engineers who took this problem on. Saw that gap and said,
we wanna fill it. They came to me for potential
solutions to fill this gap. And that’s our team,
these are the, I call them kids, they’re actually 25 years or
older. Kevin, Pratik, Michael,
brilliant kids, engineers. Had no idea about biology,
but knew that they liked the problem,
and they wanted to solve it. And these are some of the other
advisors on this team. So what is their innovation? What is Dyson’s innovation? They said okay, we need to
exclude the duodenal lining from coming into contact with food. We’ve seen the problems
with the sleeve. We don’t like burning
the duodenum and remodeling. Why don’t we put
the lining in a capsule? Why don’t we just have
the patient swallow and have the capsule release something
that will coat the duodenum? Not only coat it but
stick to it, stick to it in a way that mimics
the effect of the lining. And in fact, that’s the essence
of their innovation. So basically it’s envisioned as
a once day capsule taken each morning and filled with a fast
dissolving mucoadhesive polymer. So mucoadhesive means something
that adheres to the mucous lining of the duodenum. And essentially, this would be
a pill, but it’ll be a pill without any side effects because
this lining is not absorbed. This lining just sticks
to the duodenum, and after a few hours or
after 12 hours, is washed out, and then you start
all over again. So it’s not really a drug,
in fact, this will be classified
by the FDA as a device, because it’s not really acting
in the way a drug does. So here’s what it looks like
in actual rat intestine. This was delivered via tube
placed in the rat’s duodenum. And a few hours later,
we tagged this polymer with a green fluorescent label,
so you can actually see it. This the duodenum,
here is the lining. And this is the polymer that is
basically forming a sleeve, but a sleeve that was formed
at the site of action, not something that was placed
surgically or endoscopically. So we initially did some
studies in healthy rodents, to see whether it worked. And healthy rodents are very
difficult to actually show an effect,
because they’re not diabetic. But we were still encouraged by
what we saw, that compared to controls, there seemed to be a
flattening of the sugar levels. After ingestion of a standard
glucose challenge, this is your standard
glucose tolerance test. Then we took this
a step further, did this in diabetic rats. There is a diabetic rat called
the Zucker Diabetic Fatty rodent, and this is one of the
most commonly studied models of type 2 diabetes. And again, we saw a significant
improvement in the sugar levels. And these are most
recent results, they’ve now reproduced
this many, many times. And so what we have is
a potential solution that mimics the effects
of gastric bypass. The primary ingredient, like I
said, is not absorbed in the GI tract, which is one reason it
will be treated as a device. And in fact, the primary
component that we’ve used for these studies has a GRAS label,
which as you know stands for generally regarded
as safe by the FDA. So it may even not require much
in terms of the regulation. So in conclusion, this is
an exciting time for innovation, arguably one of the biggest
medical problems in the world. Bariatric surgery has done
us a great service, and it’s often a crude start to what’s
truly innovative in medicine. It pointed us in
the right direction. It has defined not only the gut
as the primary target but a very specific region in
the gut, the duodenum, as being a key player in this potential
solution for type 2 diabetes. And future innovations,
including what I showed you today, will utilize this
knowledge and provide access to an entirely new platform for
tackling type 2 diabetes and really benefit millions of
patients across the world. So I’ll take some questions, but
I just wanna acknowledge our sponsors and partners who
helped make this happen. A lot of the funding sources,
National Science Foundation, NIH too, SBIR STTR program,
Coulter Foundation. And this, of course, is the program through which
the students graduated. Thank you very much.

One thought on “Treating Type 2 Diabetes without Surgery or Drugs | Pankaj “Jay” Pasricha, M.B.B.S., M.D.

  1. Guys. cure your diabetes naturally does not need to be hard (I used to think it did). I will give you some tips now. Get a popular diabetes home remedy called Hybetez Remedy (just search it on google). Thanks to it I have eliminated my hypertension problem for good with healthy approaches. I shouldn't even be speaking about it cause I do not really want lots of other guys out there running exactly the same game but whatever. I am just in a great mood right now and so I'll share the wealth lol.

Leave a Reply

Your email address will not be published. Required fields are marked *